Summary

Purpose of review: The current review focuses on the therapeutic use of nanoparticles in head and neck cancer (HNC), highlighting nanoparticles at the most advanced clinical development stages.

Recent findings: Literature review covers the three main approaches for therapeutic use of nanoparticles in HNC: first, enhancing radiotherapy effect; second, performing targeted delivery of chemotherapy, immunotherapy, or genome editing molecules; third, photothermal therapy.

Summary: Nanoparticles are spherical nanoscale objects that have application in cancer therapies. Nanoparticles have diverse and often composite structure composition to ensure their function, increase their bioavailability in tumor tissues, and decrease off-target effects, sometimes by means of activating internal or external stimuli. Hafnium oxide nanoparticles are being tested in phase I to III trials for radiotherapy enhancement. Nanoparticle-based delivery of paclitaxel, cisplatin, and of the immune activator CpG-A DNA is being evaluated in phase II trials. No nanoparticle is currently approved for HNC treatment.

Summary

Purpose: This phase I study assessed the safety of first-in-class radioenhancer nanoparticles, NBTXR3, in elderly or frail patients with locally advanced head and neck squamous cell carcinoma (HNSCC), ineligible for chemoradiation.

Methods: Patients with stage III or IVA (American Joint Committee on Cancer (AJCC) guidelines, 7th edition, 2010) HNSCC of the oral cavity or oropharynx, aged ≥70 or ≥65 years and ineligible to receive cisplatin, amenable to radiotherapy (RT) with curative intent, received NBTXR3 as a single intratumoural (IT) injection followed by activation by intensity-modulated radiation therapy (IMRT; 70 Gy). The NBTXR3 dose corresponded to a percentage of the baseline tumour volume, measured by magnetic resonance imaging. The primary objectives were to determine the recommended phase II dose (RP2D), dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Safety and tolerability were assessed using National Cancer Institute CTCAE version 4.0. Antitumour activity was assessed by Response Evaluation Criteria in Solid Tumours 1.1.

Results: Nineteen patients were enrolled: 3 at the dose level of 5%, 3 at the dose level of 10%, 5 at the dose level of 15% and 8 at the dose level of 22% of the tumour volume. The MTD was not reached, and no DLTs or serious adverse event (SAEs) related to NBTXR3 were observed. Four adverse events related to NBTXR3 and/or the IT injection were reported (grade I–II). NBTXR3 remained in the injected tumour throughout RT, with no leakage in the surrounding healthy tissues. Specific RT-related toxicity was as expected with IMRT. The RP2D was determined as 22% baseline tumour volume. Preliminary signs of antitumour activity were observed.

Conclusion: Intratumoural injection of NBTXR3 followed by IMRT is feasible and demonstrated a good safety profile, supporting further evaluation at the RP2D in this patient population.

Summary

Since the discovery of cisplatin about 40 years ago, the design of innovative metal-based anticancer drugs is a growing area of research. Transition metal coordination complexes offer potential advantages over the more common organic-based drugs, including a wide range of coordination number and geometries, accessible redox states, tunability of the thermodynamics and kinetics of ligand substitution, as well as a wide structural diversity. Metal-based substances interact with cell molecular targets, affecting biochemical functions resulting in cancer cell destruction. Radionuclides are another way to use metals as anticancer therapy. The metal nucleus of the unstable radionuclide becomes stable by emitting energy. The biological effect in different tissues is obtained by the absorption of this energy from the radiation emitted by the radionuclide, the principal target generally agreed for ionizing radiations being DNA.

A new area of clinical research is now emerging using the same experimental metal elements, but in a radically different manner: metals and metal oxides used as crystalline nanosized particles. In this field, man-made functionalized nanoparticles of high electron density and well-defined size and shape offer the possibility of entering cancer cells and depositing high amounts of energy in the tumor only when exposed to ionizing radiations (on/off activity). These nanoparticles, such as hafnium oxide engineered as 50 nmsized spheres, functionalized with a negative surface (NBTXR3 nanoparticles), have been developed as selective radioenhancers, which represents a breakthrough approach for the local treatment of solid tumors. The properties of NBTXR3 nanoparticles, their chemistry, size, shape and surface charge, have been designed for efficient tumor cell uptake. NBTXR3 brings a physical mode of action, that of radiotherapy, within the cancer cells themselves. Physicochemical characteristics of NBTXR3 have demonstrated a very promising benefit-risk ratio for human healthcare across a broad non-clinical program. NBTXR3 has entered clinical development in therapy of advanced soft tissue sarcomas and head and neck cancer.